: Prostate cancer is the most common cancer and the second leading cause of cancer death in American men. The American Cancer Society estimates approximately 180,400 new cases of prostate cancer will be diagnosed and 31,900 men will die of this disease during 2000 in this country. Early detection is probably one of the most important and effective strategies for combating this major disease. PSA is the most useful marker for detection of prostate cancer. However, the specificity is still not sufficient, even though the PSA test has recently been greatly improved. About 75 percent of the men who undergo prostate needle biopsies for mildly elevated PSA values do not have prostate carcinoma. The aim of this project is to continue the efforts to develop and improve new tests for the detection of prostate cancer. Highly specific and sensitive immunoassays for serum human kallikrein 2 (hK2) have been developed for prostate cancer detection. The applicant showed the levels of hK2, a prostate-specific secretary protein, are not well correlated with the levels of PSA in prostate cancer patients, indicating that hK2 is potentially a useful marker. Furthermore, preliminary studies suggest that hK2 may also aid in cancer detection because the applicant showed that the percentfree PSA (FPSA) and total hK2/FPSA can increase the specificity of cancer detection when PSA is 2-4 ng/ml. The applicant proposes to perform a prospective study to demonstrate the usefulness of an hK2 test for prostate cancer detection. He will also study whether an hK2 test will be useful for monitoring and managing prostate cancer patients treated by chemotherapies or prostatectomies. Moreover, the applicant has cloned a PSA splicing varient (PSA-v), which supposedly produces a secreted variant of the PSA protein with a different C -terminal sequence from the wild type PSA. He will develop highly sensitive and specific immunoassays for PSA-v in order to enhance the performance of current PSA tests and to reduce the number of unnecessary biopsies.